Covalent and Noncovalent Targeting of the Tcf4/ß-Catenin Strand Interface with ß-Hairpin Mimics.

ABSTRACT

ß-Strands are a fundamental component of protein structure, and these extended peptide regions serve as binding epitopes for numerous protein-protein complexes. However, synthetic mimics that capture the conformation of these epitopes and inhibit selected protein-protein interactions are rare. Here we describe covalent and noncovalent ß-hairpin mimics of an extended strand region mediating the Tcf4/ß-catenin interaction. Our efforts afford a rationally designed lead for an underexplored region of ß-catenin, which has been the subject of numerous ligand discovery campaigns.